The EDEM3 Knockout A2780 Polyclonal Cells are a CRISPR/Cas9-mediated polyclonal knockout population in the A2780 human ovarian cancer cell line, offering a loss-of-function model for EDEM3, an endoplasmic reticulum (ER) mannosidase involved in ER-associated degradation (ERAD). This heterogeneous cell pool enables study of EDEM3??s role in glycoprotein quality control without clonal artifacts.
The A2780 line, derived from an untreated ovarian endometrioid adenocarcinoma patient, serves as a standard model for ovarian carcinoma, drug resistance, and cancer biology. Its use here provides a relevant background for dissecting protein processing pathways in a malignant context.
EDEM3 trims mannose residues from misfolded glycoproteins, generating a signal recognized by lectins OS9 and XTP3-B for targeting to the HRD1 ubiquitin ligase complex containing SEL1L and DERL1, leading to proteasomal degradation. ER stress sensors ATF6, IRE1, and PERK transcriptionally upregulate EDEM3, linking the unfolded protein response to ERAD. Thus, EDEM3 is a critical node in maintaining ER proteostasis, and its disruption impedes clearance of aberrant proteins.
In ovarian cancer, dysregulated ERAD contributes to drug resistance and tumor survival. The EDEM3 knockout in A2780 cells permits investigation of how impaired mannose trimming affects ER stress pathways, glycoprotein degradation, and cellular responses to chemotherapeutics, shedding light on proteostasis-dependent resistance mechanisms.
This model is suitable for western blotting of EDEM3 and ERAD substrates, RT-qPCR of UPR markers, flow cytometry for surface glycoproteins, ER stress reporter assays, co-immunoprecipitation with OS9/SEL1L/HRD1, and drug sensitivity testing. For further information, contact Ascent Research.
